Hypomagnesemia as an Underrecognized Adverse Effect of Long-Term Proton Pump Inhibitor Therapy: Literature review

Abstract

Proton pump inhibitors (PPIs) are among the most widely prescribed medications globally, used for the management of gastroesophageal reflux disease, peptic ulcer disease, and Helicobacter pylori eradication. While generally regarded as safe, long-term PPI use has been increasingly associated with adverse metabolic effects, among which hypomagnesemia remains one of the most underrecognized complications. Evidence consistently demonstrates that long-term PPI use impairs intestinal magnesium absorption through interference with TRPM6 and TRPM7 transporter channels. Prevalence of hypomagnesemia among long-term PPI users ranges from 13% to over 50% across studies, with higher rates in elderly patients, those on diuretics, and those on high-dose or prolonged therapy. Clinical manifestations range from subtle neuromuscular symptoms to life-threatening cardiac arrhythmias, and the condition is frequently misattributed to other causes. Despite a 2011 FDA safety warning, routine magnesium monitoring remains inconsistent and largely inadequate in clinical practice. Routine monitoring of serum magnesium in patients on prolonged PPI treatment is strongly warranted and should be incorporated into updated prescribing guidelines.